采用mTOR免疫抑制治疗肝门部及肝内胆管癌的移植治疗

Transplantation for Peri-Hilar and Intrahepatic Cholangiocarcinoma With mTOR Immunosuppression.

作者信息

Semaan Samar, Connor Ashton A, Saharia Ashish, Kodali Sudha, Elaileh Ahmed, Patel Khush, Soliman Nadine, Basra Tamneet, Victor David W, Simon Caroline J, Cheah Yee Lee, Hobeika Mark J, Mobley Constance M, Dhingra Sadhna, Schwartz Mary R, Maqsood Anaum, Heyne Kirk, Abdelrahim Maen, Li Xian C, Javle Milind, Vauthey Jean-Nicolas, Gaber A Osama, Ghobrial R Mark

机构信息

Department of Surgery, Houston Methodist Hospital, Houston, TX.

Department of Surgery, Houston Methodist Hospital, Houston, TX; Department of Surgery, Weill Cornell Medical College, New York, NY.

出版信息

Transplant Proc. 2025 Mar;57(2):255-263. doi: 10.1016/j.transproceed.2025.02.001. Epub 2025 Feb 12.

DOI:10.1016/j.transproceed.2025.02.001

PMID:39939239

Abstract

BACKGROUND

Cholangiocarcinoma (CCA) has rising incidence and mortality rates. Outcomes from combination systemic, loco-regional therapy (LRT) and liver transplantation (LT) are improving, but more granular data are needed to inform evidence-based management, including patient selection and immunosuppression.

METHODS

Patients with peri-hilar (PH) and intrahepatic (IH) CCA who underwent LT at a single center between January 2008 and February 2023 were reviewed retrospectively. Primary outcomes were overall survival (OS) and recurrence-free survival (RFS) with significance determined by Cox proportional hazards model.

RESULTS

During the study period, 53 patients underwent LT for either PH (n = 27), or IH (26). Cohort had mean age 58.5 years old (IQR, 47.0-63.0), body mass index (BMI) 25.9 (IQR, 22.9-30.0) kg/m, and mean biologic MELD 9 (IQR, 7-17). Most frequent etiology was PSC (n = 12, 22.6%). Forty-nine patients (92.5%) received neoadjuvant therapy, including systemic (n = 48, 90.6%) and locoregional therapy (LRT) (n = 22, 41.5%), to which PH tumors were both most and least responsive (P = .03). On explant pathology, tumor were a median size of 3.5 cm and lympho-vascular invasion (LVI) was present in 13 (24.5%) cases. Median follow-up post-transplant was 910 days (IQR, 407-1509). Probabilities of OS and RFS at 3-years post-LT were 69.2% (95% CI, 56.9%-84.2%) and 57.4% (95% CI, 43.7%-75.4%). In multivariable analysis, OS was associated with tumor type and LVI, and RFS with age, BMI, PSC and LRT. After a median post-LT period of 38 days (IQR, 27-79.5), 39 (71.7%) patients started mTOR inhibition with lowered tacrolimus goal. Cox proportional hazard model showed significant association of OS with mTOR inhibition, though this was not validated by a time-dependent co-variate approach.

CONCLUSIONS

In this single center cohort of CCA, post-LT outcomes were significantly greater for patients with IH tumors and no LVI. Immunosuppression with mTOR inhibition was not consistently associated with outcomes.

摘要

背景

胆管癌（CCA）的发病率和死亡率呈上升趋势。全身联合局部区域治疗（LRT）和肝移植（LT）的治疗效果正在改善，但需要更详细的数据来为循证管理提供依据，包括患者选择和免疫抑制。

方法

回顾性分析2008年1月至2023年2月在单一中心接受LT的肝门周围（PH）和肝内（IH）CCA患者。主要结局为总生存期（OS）和无复发生存期（RFS），通过Cox比例风险模型确定其显著性。

结果

在研究期间，53例患者接受了LT，其中PH CCA患者27例，IH CCA患者26例。队列的平均年龄为58.5岁（四分位间距，47.0 - 63.0岁），体重指数（BMI）为25.9（四分位间距，22.9 - 30.0）kg/m²，平均生物梅奥终末期肝病模型（MELD）评分为9（四分位间距，7 - 17）。最常见的病因是原发性硬化性胆管炎（PSC）（n = 12，22.6%）。49例患者（92.5%）接受了新辅助治疗，包括全身治疗（n = 48，90.6%）和局部区域治疗（LRT）（n = 22，41.5%），PH肿瘤对其反应最强和最弱（P = 0.03）。在切除标本病理检查中，肿瘤的中位大小为3.5 cm，13例（24.5%）病例存在淋巴血管侵犯（LVI）。移植后的中位随访时间为910天（四分位间距，407 - 1509天）。LT后3年的OS和RFS概率分别为69.2%（95%置信区间，56.9% - 84.2%）和57.4%（95%置信区间，43.7% - 75.4%）。在多变量分析中，OS与肿瘤类型和LVI相关，RFS与年龄、BMI、PSC和LRT相关。在LT后的中位时间38天（四分位间距，27 - 79.5天）后，39例（71.7%）患者开始使用mTOR抑制剂并降低他克莫司目标浓度。Cox比例风险模型显示OS与mTOR抑制存在显著关联，尽管这未通过时间依赖性协变量方法得到验证。